Our research group is interested in deciphering fundamental principles that govern genome architecture and to explore how changes in nuclear compartmentalization and the distribution of epigenetic factors alter gene expression and cellular fate. To understand epigenetic mechanisms, we primarily use X chromosome inactivation (XCI) as a model system. XCI is a fundamental gene regulatory process that takes place in early embryonic development to compensate the imbalance of X-linked gene dosage between XX females and XY males. 

Once established, the inactive X will be clonally propagated in daughter cells as heritable epigenetic memory. Both active and inactive X chromosome territories carry the same genetic code, yet their structural, molecular and gene expression profiles are profoundly different. Initiation of XCI is essential for the survival and development of female embryos while its maintenance in adult tissues is required to regulate cell identity and physiology. Its dysregulation leads to severe diseases, including immune diseases and cancer by partial or complete X chromosome reactivation.

Our work has uncovered that Xist forms nanosized supramolecular complexes (SMACs) that regulate the initiation of silencing on the inactive X. SMACs arise from only few RNA molecules, form novel protein-protein interactions that are essential to their function and regulate broad genomic regions. A major unanswered question is how these RNA-seeded supercomplexes change and mature to initiate and maintain transcriptional shutdown during development and then how these are disrupted in pathologies. To address these questions we integrate genetic engineering, biochemistry and molecular biology approaches with cutting-edge quantitative super-resolution microscopy.